The marked insulin resistance observed in the Pima Indians could be the result of a defect at the level of insulin, the insulin receptor, metabolic pathways, or any combination of the above. By a variety of sensitive criteria, the defect does not appear to be due to insulin or the insulin receptor. The isolated adipocyte is being used as a model to detect the existence of insulin resistance in pathways of carbohydrate or lipid metabolism. Further, the degree of hyperplasia or hypertrophy in obesity is being assessed in the Pima Indians by measurement of total body adiposity and adipose cell number and cell size.